Field of the Invention
The present invention provides a novel composition and a novel method for irrigating unprepared and prepared surfaces for dental and medical procedures and, in particular, for an intra-canal medicament for endodontic irrigation, stem cell preparations, tissue regeneration, removal of smear layer, disinfection and removing pulpal tissue. The present invention provides a novel single medicament that is a bactericidal agent effective against microorganisms such as Enterococcus faecalis, Streptococcus mutans and Candida albicans. 
Description of Related Art
Root canal treatment is required when tissues in root canals are injured, infected, inflamed irreversibly (pulpitis), has abnormal growth, or is needed for restorative treatment. Bacteria destroys pulp (i.e., soft tissues occupying inner space of teeth) causing pulpal necrosis, inflammation (pulpitis), and internal granulomas or closed chronic granulomas pulpitis (i.e., abnormal growth of tissues due to bacteria and inflammation).
Pulpal inflammation including inflammation caused by microorganisms such as bacteria and fungi requires root canal therapy to eliminate these microorganisms. The root canal treatment is performed in order to remove bacteria, debris, tissues, calcifications, and organic matter from the root canal and then filling the space in order to prevent bacterial invasion and irritation into surrounding tissues. A failed root canal treatment is caused by the microorganisms that contaminate a root canal system when the microorganisms leak out from the root canal into surrounding bones which is called an apical periodontitis (i.e., apical inflammation around root apex). Typically, the dominant microorganism present in the apical periodontitis is Enterococcus faelcalis and is also one of the most commonly isolated bacteria in root canal infections.
The success of root canal (or endodontic) therapy is dependent on the removal of all tissues, debris and microorganisms from the root canal area. Treatment complication or failures may occur if pulpal tissue, infecting bacteria, and microorganisms are not eliminated completely from the root canal space and/or the dentinal tubules. Bacterial invasion of microscopic spaces in dentin, irregularities or imperfections in the dentin structure including isthmuses, ramifications, accessory canals, complex root canal systems and apical deltas, can further complicate the root canal treatment and its outcome. Pulpal calcifications, pulp stones, and calcified canals may prevent a practitioner from removing all the pulpal tissue in the root canal space affecting the success of the root canal treatment. Also, biofilms (i.e., layers of microorganisms, proteins, and polysaccharides) and a smear layer (debris from mechanical preparations) needs to be removed with all of its microorganisms eradicated. Root canal treatment is indicated to remove abnormal growth of pulpal tissue of pulp polyps (chronic hyperplastic pulpitis) and of granulomatous tissue of internal resorption caused by bacteria and inflammation.
Bacteremias, caused from the presence of bacteria in the blood after dental procedures, are a major concern to the American Dental Association (ADA), and the American Association of Orthopedic Surgeons (AAOS). The bacteria that are prevalent in endodontic infections may also cause bone infections, and both the ADA and the AAOS recommend prophylactic antibiotics to be given to patients in certain cases (e.g. total hip replacement) to prevent bacteremia and infection following denial procedures. Presently, the guidelines have changed and therefore, an orthopedic implant does not routinely require pre-medication. However, the guidelines do recommend that each patient should be evaluated based on the need for prophylactic antibiotics on a case by case basis by their dental and medical professionals.
The bacteria, Streptococcus mutans and Enterococcus faelcalis, which are prevalent in endodontic infections, are also prevalent in infections in the bones. The fungus Candida has also been found in the infections in the bones. In addition, Streptococcus mutans is one of the leading causes of infective endocarditis. Therefore, both the ADA and the American Heart Association (AHA) recommend antibiotic prophylaxis for those dental patients that may be at a risk for developing an infection when the Streptococcus mutans enters their blood streams following the dental procedures and causes bacteremia. There is a documented case in ‘Heart Lung’ publication on May 7, 1988, of streptococcus mutans that causes a hematagenous bone infection in lumbar vertebrae. Therefore, it is important to eradicate bacteria and fungi from the pulpal cavity to aid in preventing the formation of bacteremia after the dental procedures. Further, it is important to eradicate these microorganisms not only from the tooth but also from within a bony cavity or from an orthopedic prosthesis for maintaining the health of the patient. However, currently, there is no single medicament or irrigant that is bactericidal against Streptococcus mutans, Enterococcus faelcalis, and Candida. 
Currently, the practitioner uses many types of irrigants in order to chemo-mechanically prepare the root canal system for obturation and regeneration of the tissues. The present endodontic treatments require use of a combination of medicaments and irrigants for the chemo-mechanical instrumentation, cleansing, disinfection, and preparing a site for endodontic regeneration. Some endodontic irrigants are utilized for their tissue dissolving ability. For example, sodium hypochlorite is a widely used tissue dissolving agent. Sodium hypochlorite's effectiveness is dependent on its concentration and irrigation time and is highly effective at 5.25% for 40 minutes and ineffective at 1.3-2.5%. Further, antibacterial agents are either bactericidal or bacteriostatic. For example, chlorohexidine is bactericidal while a mixture of tetracycline, an acid, and a detergent (MTAD) is bacteriostatic. Furthermore, other endodontic irrigants are chelating agents like Ethylenediaminetetraacetic acid (EDTA) that remove the smear layer and decalcify dentin. In endodontic regeneration, Triple Antibiotic Paste (TAP), a combination of metronidazole, ciprofloxacin, and minocycline, is used for intra-canal disinfection which is effective at a high concentration but causes discoloration. Also, Double Antibiotic Paste (DAP), a mixture of metronidazole and ciprofloxin, is used during the endodontic regeneration due to its antibacterial properties but it also causes discoloration. Further, calcium hydroxide paste is used for its alkaline property but is ineffective in eradicating endodontic pathogens. As discussed above, the success of the root canal treatment is dependent on removing all the contents from within the root canal system before obturation. As the American Association of Endodontists (AAE) stated in 2011, in “Endodontics: Colleagues for Excellence”, “the search for an ideal material and/or technique to completely clean infected root canals continues”.
Pulp calcifications within the root canal systems are obstructions to debridement in a variety of forms. Pulp stones are isolated areas of calcifications. While other calcifications take the form of diffuse calcification and irregular linear calcifications. Calcifications and calcification blockages present a problem for the practitioner in order to successfully negotiate the canal during instrumentation. Pulpal calcifications prevent root canals to be accessed and located. Pulpal calcifications can block the canal and prevent complete instrumentation of the canal space.
Conventional endodontic intra-canal medicaments have specific limitations. For example, sodium hypochlorite and calcium hydroxide do not have the ability to eradicate all the bacteria in the root canal system. Sodium hypochlorite and calcium hydroxide need to be in direct contact for it to be effective but this is difficult to attain. The direct contact cannot be gained when there are calcifications present that are natural obstructions. Also, when chlorohexidine is mixed with sodium hypochlorite during the instrumentation, an orange-brown precipitate is formed that is hard to remove and can stain.
As another example, sodium hypochlorite can dissolve organic tissue but cannot predictably inactivate endotoxins. Also, sodium hypochlorite loses its effectiveness when it is diluted. Furthermore, it is irritating to tissues. Sodium hypochlorite is not effective against bacteria such as enterococcus faecalis in the biofilms. Calcium hydroxide, an intra-canal medicament, has some antibacterial effect but is ineffective against the enterococcus faecalis, which is the most commonly isolated microorganism found in periapical lesions of the failed root canal treatment procedures.
Additionally, ethylenediaminetetraacetic acid (EDTA) which is water soluble is effective for removing inorganic material as a chelating agent but not as an effective antibacterial agent. However, EDTA should not be used with sodium hypochlorite, as it reduces the available chloride making sodium hypochlorite not effective as an irrigant.
MTAD is a mixture of doxycycline, citric acid, and Tween 80 (a detergent) in order to remove some of the smear layer. However, it is not effective against fungi within the root canal system. Also, it can have a negative effect on the bond strength of root canal sealers when used as a final intra-canal rinse. Additionally, chlorohexidine or chlorohexidine digluconate that are both water soluble can be used for disinfection but cannot dissolve tissue.
Pulp tissues contain disulfide bonds that are derived by coupling of two thiol groups. The linkage is called as an SS bond or disulfide bridge. When the disulfide bonds are broken, cell death or apoptosis occurs. Apoptosis is needed to eradicate bacteria from the root canal during the chemo-mechanical instrumentation and to prevent bacteria from re-infecting the root canal and causing apical periodontitis. Disulfide bonds are present in bacteria as they serve as a protective role for bacteria. Further, in humans also, disulfide bonds are found in secretory proteins, lysosomal proteins, mRNA, red blood cells, white blood cells, hematopoeisis cells, fibronectin, blood vessels, immunoglobins, macrophages, neutrophils, membrane proteins, antibodies, and exoplasmic domains of membrane proteins in endoplasmic reticulum. Further, disulfide bonds are also found in nuerokeratin of the myelinated sensory nerve A fibers that can be found in the pulpal tissue. Disulfide bonds are needed for protein folding. Disulfide bond formation takes place in the endoplasmic reticulum. The soft tissue of the bony cavity contain hematopoesis cells, red blood cells, white blood cells, and blood vessels which contaon disulfide bonds.
Traditionally, the dental professional or practitioner prepares a root canal system by chemo-mechanically debriding the tissue, debris and microorganisms with the use of irrigants and medicaments. The practitioner in order to clean, debride, disinfect, and shape the pulp chamber needs to dislodge calcifications, remove pulpal tissue, remove debris, and eradicate microorganisms that are present. The dental professional uses multiple medicaments and irrigants but none of the conventional irrigants or medicaments is able to eradicate Enterococcus faecalis, Candida albicans and Streptococcus mutans successfully as a single intra-canal medicament. Likewise, in a bony cavity the soft tissue that needs to be removed is done with the intramedullary reaming which is similar to the removal of pulpal tissue by reaming during instrumentation.
Thus, there is a need for a composition and method that can effectively and efficiently dissolve tissues, remove debris, remove the smear layer, disinfect, eradicate microorganisms and dislodge calcifications in the root canal treatment, for preparing surfaces for stem cell therapy, and for endodontic tissue regeneration. Further, there is also a need for a single intra-canal medicament that is a bactericidal agent to eradicate Enterococcus faecalis, Candida albicans, and Streptococcus mutans during the root canal treatments.